The project MyBio (2017-2020) will develop an innovative value chain to derive industrial polyketides - the most versatile group of natural products - by programmed cell factories of Streptomyces albus. For this purpose, we have assembled an interdisciplinary consortium to integrate systems and synthetic biology with chemical and industrial biotechnology and to co-develop tailored strains with multi-optimized biosynthetic performance, genetic stability and robustness together with an economically viable fermentation and purification strategy. Funded by the German Minstry for Education and Research (BMBF), MyBio links a consortium of leading experts from academic research in systems biology (CeBiTec), synthetic biology (PharmBio), metabolic engineering (iSBio), a high-tech SME in bioinformatics solutions (Genedata) and the world’s largest chemical company (BASF) to develop an innovative value chain. The novel technology will be demonstrated for pamamycin, a proprietary polyketide of the consortium, which acts as anti-tuberculosis drug with a novel mode of action and is also very promising as a safe crop protection agent. The production will be scaled up and used to provide pamamycin at the gram scale for testing and industrial implementation. Technology leadership and platform potential of MyBio will be demonstrated by replication of key development steps for another high-tech polyketide to be identified during the project.
Gläser L, Kuhl M, Stegmüller J, Rückert C, Myronovskyi M, Kalinowski J, Luzhetskyy A, Wittmann C (2021) Superior production of heavy pamamycin derivatives using a bkdR deletion mutant of Streptomyces albus J1074/R2. Microb. Cell Fact. 20:111. Link.
Kuhl M, Rückert C, Gläser L, Beganovic S, Luzhetskyy A, Kalinowski J, Wittmann C (2021) Microparticles enhance the formation of seven major classes of natural products in native and metabolically engineered actinobacteria through accelerated morphological development. Biotechnol. Bioeng. 118:3076-3093. Link.
Gummerlich N, Manderscheid N, Rebets Y, Myronovskyi M, Gläser L, Kuhl M, Wittmann C, Luzhetskyy A (2021) Engineering the precursor pool to modulate the production of pamamycins in the heterologous host S. albus J1074. Met. Eng. 67:11-18. Link.
Kuhl M, Gläser L, Rebets Y, Rückert C, Sakhar N, Hartsch T, Kalinowski J, Luzhetskyy A, Wittmann C (2020) Microparticles globally reprogram Streptomyces albus towards accelerated morphogenesis, streamlined carbon core metabolism and enhanced production of the antituberculosis polyketide pamamycin. Biotechnol. Bioeng. In press. Link.
Gläser L, Kuhl M, Jovanovic S, Fritz M, Vögeli B, Erb T, Becker J, Wittmann C (2020) A common approach for absolute quantification of short chain CoA thioesters in prokaryotic and eukaryotic microbes. Microb. Cell Fact. 19:160. Link.